Title : Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors.

Pub. Date : 2010 Apr 9

PMID : 20154087






9 Functional Relationships(s)
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1 Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors. celastrol TNF superfamily member 10 Homo sapiens
2 Whether celastrol, a triterpene from traditional Chinese medicine, can modulate the anticancer effects of TRAIL, the cytokine that is currently in clinical trial, was investigated. celastrol TNF superfamily member 10 Homo sapiens
3 As indicated by assays that measure plasma membrane integrity, phosphatidylserine exposure, mitochondrial activity, and activation of caspase-8, caspase-9, and caspase-3, celastrol potentiated the TRAIL-induced apoptosis in human breast cancer cells, and converted TRAIL-resistant cells to TRAIL-sensitive cells. celastrol TNF superfamily member 10 Homo sapiens
4 As indicated by assays that measure plasma membrane integrity, phosphatidylserine exposure, mitochondrial activity, and activation of caspase-8, caspase-9, and caspase-3, celastrol potentiated the TRAIL-induced apoptosis in human breast cancer cells, and converted TRAIL-resistant cells to TRAIL-sensitive cells. celastrol TNF superfamily member 10 Homo sapiens
5 As indicated by assays that measure plasma membrane integrity, phosphatidylserine exposure, mitochondrial activity, and activation of caspase-8, caspase-9, and caspase-3, celastrol potentiated the TRAIL-induced apoptosis in human breast cancer cells, and converted TRAIL-resistant cells to TRAIL-sensitive cells. celastrol TNF superfamily member 10 Homo sapiens
6 In addition, we found that celastrol induced the cell surface expression of both the TRAIL receptors DR4 and DR5. celastrol TNF superfamily member 10 Homo sapiens
7 Gene silencing of the death receptor abolished the effect of celastrol on TRAIL-induced apoptosis. celastrol TNF superfamily member 10 Homo sapiens
8 We found that celastrol also induced reactive oxygen species (ROS) generation, and ROS sequestration inhibited celastrol-induced expression of CHOP and DR5, and consequent sensitization to TRAIL. celastrol TNF superfamily member 10 Homo sapiens
9 Overall, our results demonstrate that celastrol can potentiate the apoptotic effects of TRAIL through down-regulation of cell survival proteins and up-regulation of death receptors via the ROS-mediated up-regulation of CHOP pathway. celastrol TNF superfamily member 10 Homo sapiens